Sphingosine-1 phosphate is stored in relatively high concentrations in human platelets, which lack the enzymes responsible for its catabolism, and it is released into the blood stream upon activation of physiological stimuli, such as growth factors, cytokines, and receptor agonists and antigens. It may also have a critical role in platelet aggregation and thrombosis and could aggravate cardiovascular diseases. On the other hand the relatively high concentration of the metabolite in high-density lipoproteins (HDL) may have beneficial implications for atherogenesis. For example, there are recent suggestions that sphingosine-1-phosphate, together with other lysolipids such as sphingosylphosphorylcholine and lysosulfatide, are responsible for the beneficial clinical effects of HDL by stimulating the production of the potent antiatherogenic signaling molecule nitric oxide by the vascular endothelium. In addition, like lysophosphatidic acid, it is a marker for certain types of cancer, and there is evidence that its role in cell division or proliferation may have an influence on the development of cancers. These are currently topics that are attracting great interest amongst medical researchers, and the potential for therapeutic intervention in sphingosine-1-phosphate metabolism is under active investigation.
Published International Patent Application No. WO 2008030843 describes heterocyclic aminophosphonates and oxyphosphonates having sphingosine-1-phosphate receptor biological activity.
Published International Patent Application No. WO 2008030838 describes heteroaromatic derivatives as sphingosine-1-phosphate receptor agonists and theft preparation and use in the treatment of diseases.
Published International Patent Application No. WO 2008141013 describes Sphingosine-1-phosphate 3 receptor inhibitors for the treatment of pain.
Published International Patent Application No. WO 9202513 describes the preparation of diphenylazines as antithrombotics vasodilators, antihypertensives, and antiinflammatories.
Granted U.S. Pat. No. 7,728,014 discloses heteroaromatic compounds having biological activity at the sphingosine-1-phosphate 3 receptor.